Proton MRS detects metabolic changes in hormone sensitive and resistant human prostate cancer models CWR22 and CWR22r Journal Article
| Authors: | Le, H. C.; Lupu, M.; Kotedia, K.; Rosen, N.; Solit, D.; Koutcher, J. A. |
| Article Title: | Proton MRS detects metabolic changes in hormone sensitive and resistant human prostate cancer models CWR22 and CWR22r |
| Abstract: | 17-Allylamino, 17-demethoxygeldanamycin (17-AAG), an effective inhibitor of the heat shock protein hsp90, preferentially inhibiting tumor hsp90 compared to hsp90 from normal cells, has shown promising results against several cancers, including hormone-resistant prostate cancer. Levels of several oncogenic proteins critical to tumor growth and progression, such as androgen receptor and HER2/neu, were reduced 4 h post 17-allylamino, 17-demethoxygeldanamycin treatment. Posttreatment metabolic changes have also been observed in several tumor cell lines. In this study, total choline distributions in hormone sensitive CWR22 and hormone resistant CWR22r prostate cancer xenograft tumors in mice were measured before and at 4 h and 48 h after a single-bolus 17-allylamino, 17-demethoxygeldanamycin treatment at 100 mg/kg, using proton MR spectroscopy. Our results show that tumor total choline levels declined 4 h after the treatment for CWR22 (P = 0.001) and 48 h post treatment for CWR22r (P = 0.003). Metabolic changes, in particular of total choline intensity detected by proton magnetic resonance spectroscopic imaging (MRSI), are consistent with the observed immunohistochemistry changes, tumor growth inhibition for CWR22r (P = 0.01 at 14 days post treatment), and a constant prostate specific antigen level versus increasing prostate specific antigen for control CWR22 (P = 0.01). Metabolic changes in total choline by proton MRSI can be used as an early biomarker of response for advanced-stage prostate cancer in targeted therapy such as 17-allylamino, 17-demethoxygeldanamycin. © 2009 Wiley-Liss, Inc. |
| Keywords: | controlled study; human cell; advanced cancer; cancer growth; nonhuman; biological marker; prostate specific antigen; mouse; epidermal growth factor receptor 2; tumor markers, biological; animal experiment; animal model; patient monitoring; tumor xenograft; cell line, tumor; prostate cancer; prostatic neoplasms; cancer inhibition; xenograft; magnetic resonance spectroscopy; choline; tanespimycin; heat shock protein 90; single drug dose; androgen receptor; protons; targeted therapy; cell metabolism; androgens; 17-aag; biomarker, early detection; metabolic change; mrsi, cwr22 and cwr22r; hormone resistance; hormone sensitivity; proton nuclear magnetic resonance; benzoquinones; lactams, macrocyclic |
| Journal Title: | Magnetic Resonance in Medicine |
| Volume: | 62 |
| Issue: | 5 |
| ISSN: | 0740-3194 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2009-11-01 |
| Start Page: | 1112 |
| End Page: | 1119 |
| Language: | English |
| DOI: | 10.1002/mrm.22137 |
| PUBMED: | 19780165 |
| PROVIDER: | scopus |
| PMCID: | PMC2859036 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 30 November 2010" - "CODEN: MRMEE" - "Source: Scopus" |
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